GGIP: Structure and sequence‐based GPCR–GPCR interaction pair predictor

G Protein‐Coupled Receptors (GPCRs) are important pharmaceutical targets. More than 30% of currently marketed pharmaceutical medicines target GPCRs. Numerous studies have reported that GPCRs function not only as monomers but also as homo‐ or hetero‐dimers or higher‐order molecular complexes. Many GPCRs exert a wide variety of molecular functions by forming specific combinations of GPCR subtypes. In addition, some GPCRs are reportedly associated with diseases. GPCR oligomerization is now recognized as an important event in various biological phenomena, and many researchers are investigating this subject. We have developed a support vector machine (SVM)‐based method to predict interacting pairs for GPCR oligomerization, by integrating the structure and sequence information of GPCRs. The performance of our method was evaluated by the Receiver Operating Characteristic (ROC) curve. The corresponding area under the curve was 0.938. As far as we know, this is the only prediction method for interacting pairs among GPCRs. Our method could accelerate the analyses of these interactions, and contribute to the elucidation of the global structures of the GPCR networks in membranes. Proteins 2016; 84:1224–1233. © 2016 Wiley Periodicals, Inc.     

Model studies for isolation of G-quadruplex-forming DNA sequences through a pull-down strategy with macrocyclic polyoxazole

G-quadruplexes (G4s) are non-B DNA structures present in guanine-rich regions of gene regulatory areas, promoters and CpG islands, but their occurrence and functions remain incompletely understood. Thus, methodology to identify G4 sequences is needed. Here, we describe the synthesis of a novel cyclic hepta-oxazole compound, L1Bio-7OTD (1), bearing a biotin affinity-tag as a tool to pull down G4 structures from mixtures of G4-forming and non G4-forming DNA sequences. We confirmed that it could pull down G4s associated with telomeres, bcl-2 gene, and c-kit gene.     

The sex-determining locus in the tiger pufferfish, Takifugu rubripes

The tiger pufferfish (fugu), Takifugu rubripes, is a model fish that has had its genome entirely sequenced. By performing genomewide linkage analyses, we show that the sex of fugu is determined by a single chromosomal region on linkage group 19 in an XX-XY system.     

Exercise effect on weight and body fat in men and women

Objectives: The effect of national exercise recommendations on adiposity is unknown and may differ by sex. We examined long‐term effects of aerobic exercise on adiposity in women and men. Research Methods and Procedures: This was a 12‐month randomized, controlled clinical trial testing exercise effect on weight and body composition in men (N = 102) and women (N = 100). Sedentary/unfit persons, 40 to 75 years old, were recruited through physician practices and media. The intervention was facility‐ and home‐based moderate‐to‐vigorous intensity aerobic activity, 60 min/d, 6 days/wk vs. controls (no intervention). Results: Exercisers exercised a mean 370 min/wk (men) and 295 min/wk (women), and seven dropped the intervention. Exercisers lost weight (women, ?1.4 vs. +0.7 kg in controls, p = 0.008; men, ?1.8 vs. ?0.1 kg in controls, p = 0.03), BMI (women, ?0.6 vs. +0.3 kg/m² in controls, p = 0.006; men, ?0.5 kg/m² vs. no change in controls, p = 0.03), waist circumference (women, ?1.4 vs. +2.2 cm in controls, p < 0.001; men, ?3.3 vs. ?0.4 cm in controls, p = 0.003), and total fat mass (women, ?1.9 vs. +0.2 kg in controls, p = 0.001; men, ?3.0 vs. +0.2 kg in controls, p < 0.001). Exercisers with greater increases in pedometer‐measured steps per day had greater decreases in weight, BMI, body fat, and intra‐abdominal fat (all p trend < 0.05 in both men and women). Similar trends were observed for increased minutes per day of exercise and for increases in maximal oxygen consumption. Discussion: These data support the U.S. Department of Agriculture and Institute of Medicine guidelines of 60 min/d of moderate‐to‐vigorous physical activity.     

Egg jelly of the newt, Cynops pyrrhogaster contains a factor essential for sperm binding to the vitelline envelope

The acrosome reaction of newt sperm is induced at the surface of egg jelly and the acrosome-reacted sperm acquire the ability to bind to the vitelline envelope. However, because the substance that induces the acrosome reaction has not been identified, the mechanism by which the acrosome-reacted sperm bind to the vitelline envelope remains unclear. We found here that a Dolichos biforus agglutinin (DBA) specifically mimicked the acrosome reaction immediately upon its addition in the presence of milimolar level Ca(2+). Fluorescein isothiocyanate-labeled DBA bound specifically to the acrosomal cap of the intact sperm in the presence of a Ca(2+)-chelating agent, EDTA, suggesting that binding of DBA to the native receptor for the egg jelly substance on the acrosomal region took the place of the egg jelly substance-induced acrosome reaction. In contrast, the sperm that had been acrosome reacted by DBA treatment did not bind to the vitelline envelope of the egg whose jelly layers were removed. Subsequent addition of jelly extract caused the sperm binding to vitelline envelope, indicating that the egg jelly of the newt contains substances that are involved in not only inducing the acrosome reaction but also binding to the vitelline envelope. This is the first demonstration of the involvement of egg jelly substance in the binding of acrosome-reacted sperm to the vitelline envelope.     

Fatty acids increase the circulating levels of oxidative stress factors in mice with diet-induced obesity via redox changes of albumin

Plasma concentrations of free fatty acids are increased in metabolic syndrome, and the increased fatty acids may cause cellular damage via the induction of oxidative stress. The present study was designed to determine whether the increase in fatty acids can modify the free sulfhydryl group in position 34 of albumin (Cys34) and enhance the redox-cycling activity of the copper-albumin complex in high-fat diet-induced obese mice. The mice were fed with commercial normal diet or high-fat diet and water ad libitum for 3 months. The high-fat diet-fed mice developed obesity, hyperlipemia, and hyperglycemia. The plasma fatty acid/albumin ratio also significantly increased in high-fat diet-fed mice. The increased fatty acid/albumin ratio was associated with conformational changes in albumin and the oxidation of sulfhydryl groups. Moreover, an ascorbic acid radical, an index of redox-cycling activity of the copper-albumin complex, was detected only in the plasma from obese mice, whereas the plasma concentrations of ascorbic acid were not altered. Plasma thiobarbituric acid reactive substances were significantly increased in the high-fat diet group. These results indicate that the increased plasma fatty acids in the high-fat diet group resulted in the activated redox cycling of the copper-albumin complex and excessive lipid peroxidation.     

Work behaviors of artificial muscle based on cation driven polypyrrole

A soft actuator mimicking natural muscles (artificial muscle) has been developed using a flexible conducting polymer of polypyrrole films, which were driven by electrical stimulus in a saline solution. The work characteristics were studied under various load stresses and found to behave like natural muscles. The artificial muscles shrunk and stiffened by the positive electrical stimulus by 2-3% at the maximum force of 5 MPa, and relaxed by application of negative voltages. At larger load stresses, the artificial muscle shrunk slowly as natural muscles do. The driving current also lasted longer at larger loads, indicating that the muscle sensed the magnitude of the load stress. During contraction of the muscle, the conversion efficiency from the electrical input and mechanical output energies was estimated to be around 0.06%. The maximum volumetric work was approximately estimated to be 100 kJ m(-3). These figures are unexpectedly small compared with those of natural muscles.